Vertebrate vision, initiated by photoisomerization of the chromophore 11-cis-retinal to all-trans-retinal (atRAL) in the retina, is maintained by continuous regeneration of 11-cis-retinal through a complex enzymatic pathway known as the retinoid (visual) cycle. If the conversion or clearance of atRAL in the photoreceptor cells is disrupted, this reactive aldehyde can form toxic dimeric condensation products, including N-retinyl-N-retinylidene-ethanolamine (A2E) and A2E-like derivatives. These toxic products contribute to retinal degenerative diseases, such as Stargardt disease (STGD) and age-related macular degeneration (AMD). Thus, excessive production and slow transformation of toxic atRAL are considered as one of the key factors in initiating retinal degeneration characterized by progressive photoreceptor cell death induced by both acute and chronic light exposure.
To date, there is no effective treatment that prevents, halts, or slows down the progression of STGD, AMD, and other retinal degenerative diseases in humans. However, it has been reported that, sequestration of atRAL can reduce the accumulation of A2E-like derivatives, prevent retinal degeneration and preserve vision in animal models, and potentially in humans.
Retinylamine (Ret-NH2) is an aldehyde scavenger and an inhibitor of RPE65, a critical isomerase of the retinoid cycle. Ret-NH2 also can effectively reduce levels of free atRAL in the retinas of other animal models and holds great promise as a therapeutic agent to prevent acute light induced retinal degeneration. However, this compound has various shortcomings that limit its clinical utility.